In the absence of man-eating predators, deadly disease and plague, natural disasters, and pernicious circumstances of all sorts, human beings tend to forget that their relatively recently nascent species composes but a small twig of an eons-old phylogenetic tree, pruned and trimmed for millennia by natural selection. Surrounded by the comforting glow of refrigerators and televisions, reassured by the easy accessibility of antibiotics and the surfeit of vacuum-packed potato chips that stock our expansive grocery stores, it is easy to think of humanity as the lineage that has transcended selective pressure. However, natural selection has responded to modern-day health hazards such as HIV and atherosclerosis by favoring certain chance mutations that offer their carriers a slightly better chance of survival. Adaptive polymorphisms are evidence of significant and consequential genetic variation that operates silently, subtly, covertly—even within modern human populations.
The egalitarian distribution of athletic potential is a cliché of most competitive-sport films; moviegoers find comforting the notion that spirit and drive are greater determinants of an individual’s physical performance than body type or build. In the world of popular culture, a good coach can inspire even the scrawniest of ice-hockey players to victory, and practice and bonding can transform the most chaotic of baseball teams into champions. However, recent scientific correspondence from researchers at the University College of London (Nature, Vol. 393, p. 221) has revealed a genetic basis for endurance and muscle-building that is based more on the chance inheritance of an “insertion” allele for angiotensin-converting enzyme than on hard work and confidence.
Researchers carried out two related experiments: the first tested the insertion allele’s comparative frequency among elite high-endurance mountain climbers and among the general populace, the second examined the allele’s effect upon improvement over time of various genotypes at a repetitive elbow-flexion exercise. Although the insertion allele was at Hardy-Weinberg equilibrium in the control population (p=.5, q=.5), individuals homozygous for the allele were present in unusually high proportion among the mountain climbers, suggesting that people who possess the allele have a greater tolerance for sustained exertion and hostile environmental conditions than those with the “deletion” allele. Furthermore, those who were homozygous for the insertion allele demonstrated significant improvement over a ten-week training period in the duration for which they were able to sustain an elbow-flexing exercise, while heterozygotes improved only slightly and the physical performance of subjects homozygous for the deletion allele actually decreased.
Scientists suspect the insertion allele for angiotensin-converting enzyme causes decreased tissue activity in the skeletal muscle rennin-angiotensin system, possibly resulting in increased cardiac output or capillary density, which could alter the rate of substrate delivery and thus promote greater endurance and gradual improvement at repetitive exercises. Research into the genetics of
angiotensin-converting enzyme has prompted further interest the manner in which genetic polymorphisms in humans may influence the physical ability and comparative fitness of individuals.One of the greatest threats to the survival of the inhabitants of countries in which high-cholesterol food is plentiful and cheap is atherosclerosis, a medical condition that involves the accumulation of fatty substances, calcium, and cell waste products upon the inner walls of arteries. These deposits (also known as “plaques”) reduce the elasticity and diameter of arterial walls, resulting in reduced room for blood flow and, therefore, increased blood pressure (much as a clogged pipe whose diameter is reduced by a build-up of sediment is put under structural strain by the undiminished volume of flowing water.)
In the 1980s, a plaque-reducing allele for
apolipoprotein, a lipid-binding protein which removes cholesterol from cells, was discovered in approximately fifty inhabitants of a small Italian town near Milan. These individuals enjoyed rich foods and a high-cholesterol diet, yet never suffered the negative symptoms commonly associated with such a lifestyle. Though their blood cholesterol levels remained high, there was no sign of any corresponding hardening of arteries. Evidently, this mutated form of apolipoprotein (commonly known as apolipoprotein A-1 Milano) inhibits the progression of atherosclerosis, reduces the arterial inflammation and damage associated with atherogenesis, and is even capable of stimulating faster and more effective removal of lipids from arterial tissue, thereby reducing the risk of vascular disease. Quite by chance, random mutation, a generator of genetic innovation and a common mechanism for adaptive evolution, has produced an antidote for hazardous eating habits and unhealthy diets.Several modern human innovations—such as refrigeration, improved sanitation measures, and advances in immunology and bacteriology research—have contributed to the relatively disease-free lives we lead: in many parts of the world, typhoid fever, dysentery, smallpox, and tuberculosis are vanquished foes. Unfortunately, new and menacing threats have arisen to take their place, among them AIDs and HIV—two of the greatest health threats facing modern nations, both developed and undeveloped.
Though most medical treatments have proven ineffective for those infected with AIDs or HIV, a
32 base-pair deletion in the gene CKR5, which codes for a truncated and defective version of one of the two receptors on the surfaces of T-cells and macrophages that enables HIV to fuse with the cell membrane, appears to provide homozygotes with incomplete resistance to the virus. The mutant allele has a frequency of 0.10 in Caucasian-European populations, far higher than the frequency among African and East-Asian populations (0.017 and 0.00, respectively), indicating a recent European origin for the mutation—most likely in Sweden, where the allele is present in a frequency of 0.137, higher than any other nation in Europe (Human Molecular Genetics. 1998 Mar;7(3):399-406). Models of haplotype coalescence indicate a selective event approximately 700 years ago, possibly related to the Black Plague ( Yersenia pestis), which depends upon the same macrophage receptors as HIV-1 for its proliferation. In short, a human genetic polymorphism that originally protected Europeans from the Black Plague is still selected for today, protecting its carriers from infection by HIV.For most of us, the struggle for survival is no longer an oppressive and conspicuous (or even detectable) aspect of our everyday existence. Differential reproductive success may no longer be a matter of fighting off carnivorous predators, escaping natural disasters, or warding off malnutrition and malnourishment—it may simply be a personal preference. Nevertheless, genetic variation and selective pressure, the two central components of adaptation and evolution, exert their influence upon human populations to this day.